Pharmaceutical formulation comprising a phosphodiesterase inhibitor

Abstract

Pharmaceutical formulations to be administered by pressurized metered dose inhalers (pMDIs), comprising a compound of general formula (I) may be used for the treatment and/or prevention of inflammatory or obstructive airway diseases.

The invention claimed is: 
     
       1. A pharmaceutical formulation for aerosol administration, comprising:
 (a) the (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester; 
 (b) a propellant; 
 (c) a co-solvent; and 
 (d) a surfactant selected from the group consisting of a PEG surfactant, a PVP surfactant, and a mixture thereof. 
 
     
     
       2. A formulation according to  claim 1 , which is in the form of suspension. 
     
     
       3. A formulation according to  claim 1 , wherein said surfactant is selected from the group consisting of PEG 600, PVP (K25), and a mixture thereof. 
     
     
       4. A pharmaceutical formulation according to  claim 1 , wherein said co-solvent is ethanol. 
     
     
       5. A formulation according to  claim 1 , which comprises said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester in an amount of 0.02 w/w to 0.7 w/w, based on the total weight of the formulation. 
     
     
       6. A formulation according to  claim 1 , wherein said propellant is a hydrofluoroalkane selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, and a mixtures thereof. 
     
     
       7. A pressurized metered dose inhaler (pMDI), containing a formulation according to  claim 1 . 
     
     
       8. A method of treating inflammatory or obstructive airway disease, comprising administering an effective amount of a formulation according to  claim 1  to a subject in need thereof. 
     
     
       9. A method according to  claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 10 μg to 2000 μg. 
     
     
       10. A method according to  claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 20 μg to 1000 μg. 
     
     
       11. A method according to  claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 50 μg to 800 μg. 
     
     
       12. A method according to  claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 80 μg to 700 μg. 
     
     
       13. A method according to  claim 8 , wherein said (−) enantiomer of 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester is administered at a daily therapeutically effective dose of 300 μg to 600 μg. 
     
     
       14. A formulation according to  claim 1 , which comprises said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester having an optical purity higher than 95% w/w, based on the weight of said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester. 
     
     
       15. A formulation according to  claim 1 , which comprises said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester having an optical purity higher than 98% w/w, based on the weight of said 3-cyclopropylmethoxy-4-methanesulfonylaminobenzoic acid 1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(3,5-dichloro-1-oxypyridin-4-yl)ethyl ester.